Protective Effect And Mechanism Of Yiqi Huoxue Chinese Medicine On Myocardium In Old Myocardial Infarction And Chronic Heart Failure Rats

Part 1Qishen Capsule Promotes Cardioprotective Efficacy in Rats with Chronic Myocardial InfarctionBackground:Qishen Capsule (QSC), a traditional Chinese medicine, has been widely used to treat coronary heart disease in China, whereas the evidence supporting its efficacy remains unclear. To explore whether QSC can have cardioprotective efficacy after myocardial infarction (MI), we design this experiment in a preclinical model of myocardial infarction in rats.Methods:4 weeks after left anterior descending coronary artery ligation, rats received either intragastric administration of QSC, or the same volume of saline. Cardiac function was assessed echocardiographically. Angiogenesis and apoptosis were detected using histology and western blot methods four weeks after QSC therapy.Results:Reductions in infarction area and scar collagen content in MI+QSC group were observed in the infarct region compared with the saline control. Echocardiographic and hemodynamic analyses also demonstrated relatively preserved cardiac function after QSC treatment. QSC significantly decreased apoptosis relative to control group, evidenced by influencing the expression of bcl-2、Bax、cytochrom C and caspase3 in the myocardial infarction. Meanwhile, angiogenesis in the infarctive regions were significantly enhanced relative to control group, evidenced by increased density of α-smooth muscle actin and CD31 positive vessels respectively. Similarly, the mRNA expressions of VEGF and HIF-1α were up-regulated. Additionally, QSC involvement also increased the phosphorylation of AKT and down-regulated the phosphorylation of MEK/ERK.Conclusions:QSC therapy can improve cardiac function in rats after MI, the underlying mechanism of which can be explained by increasing angiogenesis, reducing apoptosis partially via the activation of AKT signaling pathway and inhibition of phosphorylation of MEK/ERK.Part 2Panax Notoginseng Saponins Promotes Cardioprotective Efficacy in Rats with Chronic Myocardial InfarctionBackground Panax notoginseng saponins (PNS) are one of the most important compounds derived from roots of the herb Panax notoginseng which are frequently used in the area of cardiovascular protection. Meanwhile, angiogenesis offers the potential for treating ischemic cardiomyopathy. The aim of this study was to elucidate whether PNS can boost cardiac function and angiogenesis and to determine its regulatory mechanisms after Myocardial Infarction.Methods 4 weeks after left anterior descending coronary artery ligation, rats received either intraperitoneal injection of PNS, or the same volume of saline. Cardiac function was assessed by echocardiographic and hemodynamic analyses, and angiogenesis was assessed histologically four weeks after therapy.Results Reductions in infarction area and scar collagen content were observed by improvements in left ventricular function and attenuation of left ventricle remodeling that were observed histologically in the infarct region compared with the saline control. Echocardiography also showed significant improvements in ejection fraction and fractional shortening in the PNS group. Meanwhile, angiogenesis in the infarctive region was significantly enhanced relative to control group, evidenced by increased density of α-smooth muscle actin (α-SMA) and CD31 positive vessels respectively. Similarly, the mRNA expressions of VEGF and HIF-1α were up-regulated. Furthermore, the phosphorylation of MEK/ERK was enhanced after the treatment with PNS.Conclusion In conclusion, these results show for the first time that PNS can increase angiogenesis and preserve cardiac function at least in part through the Akt pathway, which provides a novel explanation for the multi-function of PNS on cardiovascular system.Conclusion In conclusion, these results show for the first time that PNS can increase angiogenesis and preserve cardiac function at least in part through the Akt pathway, which provides a novel explanation for the multi-function of PNS on cardiovascular system.Part 3Effects of Xinfuli granula on Cardioprotective Efficacy in Rats with Heart FailureObjective:To investigate the effects of Xinfuli granula on myocardial energy metabolism in rats with heart failure (HF).Methods:60 male SD rats were randomly divided into 5 groups:normal control group, HF group, low-dose xinfuli granula group, medium-dose xinfuli granula group and high-dose xinfuli granula group. All the groups were injected intraperitoneally with adriamycin except normal control group with isovolumic normal saline for 6 weeks. Then experimental rats were given the corresponding drugs by intragastric injection for 4 weeks (low-dose group:0.675g/(kg·d), n=12; medium-dose group:1.350g/(kg. d), n=12; high-dose group:2.700g/(kg. d), n=12). Normal control group and HF group were perfused with the same volume of saline as the medium-dose group. The expressions of peroxisome proliferator activated receptor-α (PPAR-α) and endothelin-1 (ET-1) were measured by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immuno sorbent assay (ELISA) respectively.Results:The data from the PCR analysis showed that PPAR-α mRNA expression levels were significantly up-regulated in low medium and high dose Xinfuli groups as compared with the model group (P<0.05). Meanwhile, the low medium and high dose Xinfuli groups exhibited markedly decreased ET-1 levels (P<0.01) as detected by ELISA.Conclusion:Our findings suggest that xinfuli granula can improve the cardiac function and myocardial energy metabolism in the HF rats induced by adriamycin, and the underlying mechanism may be related to its effects on the expression of PPAR-α...